Bigger than Any Transplant Story You’ve Heard Before…

September 29, 2010|36,771views

Dr. Gabor Forgacs is one of the leading experts in the world in the area of what is now called “organ printing,” where aggregates of cells for a particular organ are delivered with an ordinary (but modified) inkjet printer onto biological scaffolding gels (the “paper”).

Dr. Forgacs is a biophysicist with degrees in biology as well as advanced physics and is currently heading up a biophysics lab called Forgacslab at the University of Missouri-Columbia. His research focuses on the physical mechanisms in cellular and developmental biology.

The number of people in need of organ transplants continues to rise faster than the number of available donors, and as a result, 19 people die every day due to the shortage.

As of February 10, 2010, there were over 105,600 people waiting for an organ donation in the United States. However, from January to November 2009, just over 26,000 organ transplants took place.

So it would be nothing short of miraculous if we could one day replace virtually every organ or tissue in patients’ bodies with young pristine organs, as they age or become diseased or injured.

Recently, steps toward achieving this goal have advanced greatly, thanks in part to the amazing work pioneered by Dr. Gabor Forgacs.

“Beam Me a New Lung, Scottie”

Printing tissues and organs may seem like science fiction, but it really isn’t anymore.

Ordinary inkjet printers are now being modified to deposit biological material, including human cells, in a controlled and efficient manner.

Dr. Forgacs hopes to be able to use his organ printer to eventually build full-sized, fully functional organs that can be surgically implanted in your body. These organs might not look anything like the ones you have now, but they will perform the same functions.

Of course, fully functional laboratory-grown hearts and livers are a future possibility, but that level of complexity is out of reach, for now.

Forgacs’ current focus is on tubular constructs that can be used to replace blood vessels. The rational for this is, every organ and tissue must have vascularization to survive, so this is a crucial step before more complex tissues can be created.

The tubular constructs can also be used for hemodialysis and peripheral bypass surgery, and will eventually be used in coronary bypass surgery once standards of safety are met.

Building a Better Blood Vessel

A blood vessel may not seem like a highly complex organ, but it actually involves growing three different types of cells in a multi-phased process:

A biopsy is taken from the patient. Ordinary skin cells are used to provide the basis for the fibroblastic layer (the outer layer of the vessel). Other cells that must be obtained are endothelial cells from the innermost part of the patient’s blood vessel, and smooth muscle cells, which provide elasticity.

The various cells are then grown in Petri dishes, and they create their own extracellular matrix. This matrix is an important component of every organ, making up the frame of the organ to which the other cells attach.

The sheet of cells is then wrapped around a Teflon tube. The cells don’t attach to the tube, but knit together around it, after which they can slide the Teflon tube out, leaving a tubular vessel.

Alternately, some companies choose to use the patient’s cells along with an artificial scaffold material, providing a synthetic extracellular matrix, instead of waiting for the cells to make their own matrix. However, this procedure has yielded less than spectacular results, apart from a few successes.

Printing Out New Nerves

One of the applications of blood vessel-type structures is nerve grafts, which Dr. Forgac’s lab is working on.

When you have a serious enough accident to sever a major nerve -- in a limb for example -- a laboratory-grown tube of cells can act as a bridge between the distal and proximal ends of the damaged nerve.

The human body can spontaneously regenerate gaps of 1 to 3 centimeters without any intervention, given time. However, beyond 3 centimeters, the two ends of the nerve cannot “find each other” to reconnect. A nerve bridge can help with this, and the tissues used to create the nerve bridge can be “printed” on an organ printer.

The printing process is very versatile.

Dr. Forgac has this technology up and running now, and it is just a matter of time before his team will be building sheaths of cardiac or brain tissue that can be used as patches for victims of heart attack and stroke.

Tissuing in a New Age

Eventually, as scientists master the engineering of human tissues, they will be able to build an entire kidney, or a new pancreas with islets of Langerhans-type cells that will be able to make insulin for type 1 diabetics -- making insulin pumps a thing of the past.

One huge advantage of building organs in the lab from your own cells is the lack of tissue rejection. Currently, patients who receive organ transplants are usually tethered to a lifetime of strong anti-rejection medications that have damaging side effects of their own.

But the science isn’t quite there yet.

Tissue engineering is so complex that companies are focusing on one type of tissue at a time so that they can get to the point of offering a saleable product that can sustain them financially. There are about 22 tissues and organ structures in the pipelines to date. Fortunately, there is a good deal of funding available right now for this kind of research.

Two of the most impressive recent success stories are the construction and implanting of a new trachea in one patient, and a new bladder in another.

In 2009, a team of Spanish and British researchers built a tracheal segment for a young woman who had problems breathing. The tracheal segment they built was truly a marvel of bioengineering.

They began with the trachea of a cadaver, “shaking off” the cells from the extracellular matrix. Then they used the bare matrix as a frame and populated it with stem cells from the patient so that there would be no tissue rejection. It was a real breakthrough in the sense that biological material was used from two sources and put together to make a final product.

When they inserted this new tracheal segment into the woman’s respiratory tract, it was a huge success, and she is breathing normally to this day.

Anthony Atala, one of the world’s leading tissue engineers, successfully built and implanted a bladder into a woman whose bladder was unable to function properly. This is the most complex organ that has been “grown” in a lab and transferred into a patient, to date.

Atala’s company, Wake Forest Institute for Regenerative Medicine, is also in the process of engineering a human ear.

Your Body as Bioreactor

A bioreactor is a gizmo into which you put your engineered tissue to mature, to grow into whatever form you are targeting. The bioreactor has to mimic the physiological conditions of the human body.

Machines have been developed as bioreactors. But the best bioreactor is the human body itself!

The Belgian group who built the tracheal segment did just this. They built the trachea in the lab and implanted it into the patient’s hand so that it could vascularize in the patient’s own blood supply, using her body as the bioreactor. Then once vascularized, the tracheal segment was moved into its final place -- into the damaged trachea itself.

This was a monumental bioengineering feat!

Organ Replacement Has Its Limits - The Ultimate Goal is Organ Regeneration

According to the anti-aging experts, it is unlikely we are going to be able to significantly slow down the aging process (barring some unforeseen breakthroughs). So, scientists are aiming their research toward enhancing the body’s ability for tissue and organ regeneration.

According to Dr. Forgacs, tissue engineering is really turning more toward “regenerative engineering” or “regenerative medicine,” since it is unlikely they will ever be able to grow complex organs, like a heart, in the lab and just put it into you.

They are trying to understand and capitalize on your body’s own regenerative abilities.

Your body already has an amazing ability to regenerate. The following are just a few examples:

Skin wounds and broken bones generally heal well spontaneously.

Some organs show regenerative ability, such as your liver, which can regenerate itself even if more than 75 to 90 percent of it is removed.

One man has been able to regenerate his severed fingertip. Surgeons applied a special extracellular matrix powder -- a mixture of protein and connective tissue used to repair tendons—which signaled his body to start the process of tissue regrowth. In just four weeks, the man’s fingertip grew back completely.

Right now, scientists can implant special smart biomaterials, like this matrix, to encourage your body’s tissues rebuild themselves, but this only works for small areas -- typically 1 centimeter or less. Technological advances will make it possible to not only replace entire organs, but to repair much larger areas.

And these advances are being made at increasingly impressive rates -- revealing possibilities that would have been unimaginable 20 years ago.

It’s very possible that 10 years from now, you will have the option of receiving a laboratory grown kidney that is capable of filtering waste from your body, completely free of the risk for rejection.

It seems that you and your children will be receiving an extension on the limited “organ warranties” you were born with, thanks to the pioneering work of bioengineers like Gabor Forgacs.

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